Treating the Signs of Multiple Myeloma Before it Starts

Progress in treating multiple myeloma, or cancer of the plasma cells in bone marrow, has advanced significantly over the past decade. Today, questions about the disease often involve finding a treatment that balances the goal of putting a patient into remission — especially if stem cell transplantation is a possibility – against the toxicity of the treatment itself. With the rise of more advanced targeted therapies, this balancing act involves new questions; it may make sense to identify, and treat, those patients who are only showing warning signs of the cancer.

th

Ola Landgren, MD, PhD, of the Centers for Cancer Research, opened the education session on multiple myeloma at the 55 American Society of Hematology Annual Meeting and Exposition in New Orleans by outlining the steps that occur before a patient progresses to multiple myeloma. It is during this quiet period, when a patient may be asymptomatic, that the standard of care has been to “watch and wait,” especially for damage to the kidneys or the skeletal system. But because multiple myeloma ultimately involves an elevated number of plasma cells, it disrupts the body’s immune system, and puts the patient at risk for numerous problems.

Clinicians have known the precursors to multiple myeloma for more than 30 years. In 1978, Robert A. Kyle, MD, and Philip R. Greipp, MD, of the Mayo Clinic identified monoclonal gammopathy of unknown significance, or MGUS, as a precursor to the disease; in 1980, they followed up by identifying “smoldering” multiple myeloma (SMM) as a distinct state in which a patient is at-risk of developing the cancer but without the end-organ impairment seen in the disease.

Though these precursor states have been long identified, Dr Landgren said in a companion paper to his talk that the cornerstone of disease management remains to monitor patients with bloodwork and x-rays, in part because a 1988 study of treating SMM patients with chemotherapy failed to show any significant difference in the end points of remission or survival.¹ With no apparent benefit, the toxicity of treatment for patients not exhibiting any symptoms did not make sense, Landgren explained in his talk.

But times are changing. Landgren cited the work of the next speaker, Maria-Victoria Mateos, MD, who in August published results in the New England Journal of Mediciine from her Spain-based research group's randomized phase III trial, which found that SMM patients in a group receiving a treatment of lenalidomide plus dexamethasone, followed by a maintenance regimen, had a significantly longer median time to progression than a similar group under observation.²

“These are very encouraging results,” said Dr Landgren. He said, however, that treatment of SMM must remain within clinical trials, as there are still too many unanswered questions — not the least of which is understanding the mechanism by which MGUS in plasma cells moves into SMM and finally to multiple melanoma.

“We need to better define high-risk and low-risk smoldering (multiple myeloma) patients,” he said. Dr Mateos followed with a review of treatment options for patients for whom stem-cell transplantation may not be an option, noting that many patients are elderly — the peak age for this population is older than 65.

Complete response should be a treatment objective, she said, but with elderly patients especially, that must be balanced with ensuring their quality of life, and that means paying attention to their tolerance for toxicity. Fortunately, Dr Mateos said, thalidomide, bortezomib, and lenalidomide, which allow clinicians to develop individualized treatment strategies, have created a vast array of options for treating older patients that did not exist 10 or even 5 years ago. She reviewed data from 6 recent trials and discussed a trial now underway in which elotuzumab, an anti-CSI monoclonal antibody, is in one treatment arm with lenalidomide and dexamethasone, and being compared to another arm of that drug combination alone.

Philip McCarthy, MD, of the Roswell Park Cancer Institute in Buffalo, New York, discussed strategies for treating patients both leading up to stem cell transplantation and beyond. One question for consideration: When should a transplant occur? Multiple factors come into play, into a patient’s age — which Dr McCarthy said is the “biological age,” not necessary the real age – how frail the patient is and whether renal failure has occurred.

“Higher stage disease doesn’t do as well,” he said.

As with the identification of SMM, molecular testing can play a role, as clinicians are learning more and more about markers that can help determine who is a good candidate for transplant.

Once a transplant has occurred, maintenance therapy can involve bortezomib or lenalidomide or both, depending on the patient’s level of risk. In a paper prepared ahead of the talk, Dr McCarthy concluded, “Incorporation of new agents into the continuum of multiple myeloma care should result in improved outcomes and long-term disease control.”³

References

1. Landgren O. Monoclonal gammopathy of undetermined significance and smoldering multiple myeloma: biological insights and early treatment strategies. Hematology Am Soc Hematol Edu Program, 2013; 2013:478-487.
2. Mateos MV, Hernandez MT, Giraldo P, et al. Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Eng J Med 2013;369:438-477.
3. McCarthy PL, Hahn T. Strategies for induction, authologous hematopoietic stem cell transplantation, consolidation, and maintenance for transplantation-eligible multiple myeloma patients. 496-503. Hematology Am Soc Hematol Edu Program, 2013; 2013:496-503.